Brainstem–Cerebellar Circuit Dysfunction and Structure–Function Decoupling in Body-First Parkinson’s Disease

Abstract Parkinson’s disease (PD) is heterogeneous, but imaging features of body-first PD remain incompletely characterized. In this case-control study, 54 patients were classified by probable rapid eye movement sleep behavior disorder timing relative to motor onset as body-first (n = 24) or brain-first PD (n = 30), alongside 30 healthy controls. Multimodal MRI assessed dorsal motor nucleus of the vagus (DMV)-seeded functional connectivity, local activity, regional homogeneity, cerebellar gray matter volume, and structure–function decoupling. Body-first PD showed increased DMV–cerebellar connectivity, with convergent abnormalities in bilateral lobule VIII comprising increased activity and synchrony, lower gray matter volume, and greater structure–function mismatch. Higher DMV–lobule VIII connectivity was associated with worse gait, motor, non-motor, and sleep burden after covariate adjustment. Normative Allen Human Brain Atlas analysis identified developmental and signal-regulatory enrichment. These findings suggest a DMV–lobule VIII imaging phenotype associated with clinically defined body-first PD.